Dietary macro/micronutritional supplement for patients undergoing kidney dialysis

ABSTRACT

Provided herein is a nutritional supplement designed to support kidney and cardiac function as well as mitochondrial energy function needs in patients undergoing hemodialysis. This supplement replenishes essential vitamins and minerals that are lost during dialysis, does not contain compounds that may specifically cause harm to dialysis patients, and provides support for tissues undergoing oxidative stress.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of U.S. nonprovisionalapplication Ser. No. 16/326,250, filed Feb. 18, 2019, which is a USnational phase application of international application no.PCT/US2017/048126 filed on Aug. 23, 2017, which claims priority uponU.S. provisional application Ser. No. 62/379,872, filed Aug. 26, 2016and Swedish application no. 1651259-2 filed on Sep. 23, 2016. Theseapplications are hereby incorporated by reference in their entiretiesfor all of their teachings.

BACKGROUND

The kidneys of an adult human filter approximately 190 liters of blooddaily; due to their role, these organs are susceptible to damage anddysfunction that may progress, over time, to disease. Chronic KidneyDisease:http://www.lifeextension.com/protocols/kidney-urinary/kidney-disease/page-04High blood pressure, elevated blood sugar (including the presence ofdiabetes), high-protein diets, smoking, obesity, family history ofkidney disease or failure, and a patient's history of heart problems allthreaten the health of the kidneys, inflicting damage that has thepotential to be lethal. In many cases, when the kidneys fail to performadequately, kidney dialysis is required.

Essential amino acids such as L-carnitine can be essentially lost(70-80%) during dialysis; L-carnitine deficiency is associated withmuscle aches and fatigue, confusion, hypoglycemia, cardiomyopathy, fattyliver, muscle necrosis, abnormal lipid storage, and other conditions.

Oxidative stress, which is caused by an excess of free radicals andharmful molecules that can damage basic cellular constituents such aslipids, proteins, and DNA, can result from L-carnitine deficiency and isan especially dangerous condition for patients undergoing dialysis.Inadequate energy management in cardiac tissues brought on byL-carnitine deficiency can lead to cardiovascular complicationsincluding heart attack and heart failure. Further stressors include anexcessive filtration burden on the kidneys resulting from the need tohandle advanced glycation and lipoxidation end products andinflammation, especially when kidney function decreased to the pointthat dialysis is required.

Many essential nutrients, including water-soluble vitamins such as Bcomplex vitamins and vitamin C and minerals such as zinc and seleniumare depleted from the body during dialysis treatment. Further, othernutrients such as vitamin D, which is primarily produced by the healthykidney and, in case of kidney failure, vitamin D synthesis ceases, or,is significantly affected. Other nutrients, however, such as fat-solublevitamins, can accumulate in the tissues to dangerous levels in dialysispatients and should not be supplemented.

What is needed is a nutritional supplement that can replenish the supplyof basic nutrients to the body that are lost by dialysis, withoutproviding the excess of fat soluble vitamins that could be damaging inhigh quantities. Ideally, this supplement would also provide nutrients,including but not limited to L-carnitine, that support overall kidneyhealth and combat the effects of oxidative stress. In addition toreplenishing these essential nutrients, the supplement would ideallyprovide coenzyme Q10, which is a key component of the mitochondrialelectron transport chain that is known to be important to mitochondrialenergy generation (i.e., ATP synthesis). Finally, polyunsaturated fattyacids such as, for example, marine omega 3 fatty acids, are also removedfrom the body with chronic kidney dialysis. These compounds are lipidsoluble macronutrients that are important to metabolism (i.e., energyproduction captured in the form of ATP).

The present invention addresses these needs by providing a nutritionalsupplement that will address the damaging effects of chronic kidneydialysis on the body.

SUMMARY

Provided herein is a nutritional supplement designed to support kidneyand cardiac function as well as mitochondrial energy function needs inpatients undergoing hemodialysis. This supplement replenishes essentialvitamins and minerals that are lost during dialysis, does not containcompounds that may specifically cause harm to dialysis patients, andprovides support for tissues undergoing oxidative stress.

The advantages of the materials, methods, and devices described hereinwill be set forth in part in the description that follows, or may belearned by practice of the aspects described below. The advantagesdescribed below will be realized and attained by means of the elementsand combinations particularly pointed out in the appended claims. It isto be understood that both the foregoing general description and thefollowing detailed description are exemplary and explanatory only andare not restrictive.

DETAILED DESCRIPTION

Before the present materials, articles, and/or methods are disclosed anddescribed, it is to be understood that the aspects described below arenot limited to specific compounds, synthetic methods, or uses, as suchmay, of course, vary. It is also to be understood that the terminologyused herein is for the purpose of describing particular aspects only andis not intended to be limiting.

In the specification and in the claims that follow, reference will bemade to a number of terms that shall be defined to have the followingmeanings:

It must be noted that, as used in the specification and the appendedclaims, the singular forms “a,” “an,” and “the” include plural referentsunless the context clearly dictates otherwise. Thus, for example,reference to “a citrus bioflavonoid” includes mixtures of two or morecitrus bioflavonoids, and the like.

“Optional” or “optionally” means that the subsequently described eventor circumstance can or cannot occur, and that the description includesinstances where the event or circumstance occurs and instances where itdoes not. For example, the nutritional supplements described herein mayoptionally contain turmeric, where the turmeric may or may not bepresent.

As used herein, the term “about” is used to provide flexibility to anumerical range endpoint by providing that a given value may be “alittle above” or “a little below” the endpoint without affecting thedesired result.

“Unit dose” refers to a discrete amount of formulation to beadministered to a subject. The compositions and formulations disclosedherein are packaged into discrete dosages each containing predeterminedquantities of active compounds calculated based on the needs and medicalhistory of the subject.

A “pharmaceutically-acceptable compound” is used to refer to a neutralcomplex. In some aspects, a pharmaceutically-acceptable compound may bemore economical to produce, may have increased chemical stability, mayallow manipulation of the compound's pharmacokinetics andbioavailability, may make the compound easier to administer, or acombination thereof. In a further aspect, a pharmaceutically-acceptablecompound can alter a compound's dissolution or solubility. In oneaspect, the pharmaceutically-acceptable compound can be an ioniccompound. For example, the pharmaceutically-acceptable compound can bethe reaction product between an organic acid (e.g., citric acid) andbase (e.g., calcium hydroxide) to produce the ionic compound calciumcitrate.

Throughout this specification, unless the context dictates otherwise,the word “comprise,” or variations such as “comprises” or “comprising,”will be understood to imply the inclusion of a stated integer or step orgroup of integers or steps but not the inclusion of any other integer orstep or group of integers or steps.

References in the specification and concluding claims to parts byweight, of a particular element or component in a composition orarticle, denote the weight relationship between the element or componentand any other elements or components in the composition or article forwhich a part by weight is expressed. Thus, in a compound containing 2parts by weight of component X and 5 parts by weight of component Y, Xand Y are present at a weight ratio of 2:5, and are present in suchratio regardless of whether additional components are contained in thecompound.

As used herein, a plurality of items, structural elements, compositionalelements, and/or materials may be presented in a common list forconvenience. However, these lists should be construed as though eachmember of the list is individually identified as a separate and uniquemember. Thus, no individual member of any such list should be construedas a de facto equivalent of any other member of the same list basedsolely on its presentation in a common group, without indications to thecontrary.

Concentrations, amounts, and other numerical data may be expressed orpresented herein in a range format. It is to be understood that such arange format is used merely for convenience and brevity and thus shouldbe interpreted flexibly to include not only the numerical valuesexplicitly recited as the limits of the range, but also to include allthe individual numerical values or sub-ranges encompassed within thatrange as if each numerical value and sub-range was explicitly recited.As an illustration, a numerical range of “about 1 to about 5” should beinterpreted to include not only the explicitly recited values of about 1to about 5, but also to include individual values and sub-ranges withinthe indicated range. Thus, included in this numerical range areindividual values such as 2, 3, and 4, the sub ranges such as from 1-3,from 2-4, from 3-5, etc., as well as 1, 2, 3, 4, and 5 individually. Thesame principle applies to ranges reciting only one numerical value as aminimum or maximum. Furthermore, such an interpretation should applyregardless of the breadth of the range or the characteristics beingdescribed.

Disclosed are materials and components that can be used for, can be usedin conjunction with, can be used in preparation for, or are products ofthe disclosed compositions and methods. These and other materials aredisclosed herein, and it is understood that when combinations, subsets,interactions, groups, etc., of these materials are disclosed, that whilespecific reference to each individual and collective combination andpermutation of these compounds may not be explicitly disclosed, each isspecifically contemplated and described herein. For example, if a watersoluble vitamin is disclosed and discussed and a number of differentminerals are discussed, each and every combination of water solublevitamin and mineral that is possible is specifically contemplated unlessspecifically indicated to the contrary. For example, if a class of watersoluble vitamins A, B, and C are disclosed, as well as a class ofminerals D, E, and F, and an example combination of A+D is disclosed,then even if each is not individually recited, each is individually andcollectively contemplated. Thus, in this example, each of thecombinations A+E, A+F, B+D, B+E, B+F, C+D, C+E, and C+F is specificallycontemplated and should be considered from disclosure of A, B, and C; D,E, and F; and the example combination of A+D. Likewise, any subset orcombination of these is also specifically contemplated and disclosed.Thus, for example, the sub-group of A+E, B+F, and C+E is specificallycontemplated and should be considered from disclosure of A, B, and C; D,E, and F; and the example combination of A+D. This concept applies toall aspects of the disclosure including, but not limited to, steps inmethods of making and using the disclosed compositions. Thus, if thereare a variety of additional steps that can be performed with anyspecific embodiment or combination of embodiments of the disclosedmethods, each such combination is specifically contemplated and shouldbe considered disclosed.

As used herein, a vitamin is an organic compound that is required insmall quantities to support essential body functions including growthand cellular maintenance. In some aspects, vitamins cannot be producedby the body (e.g., vitamin C) or are not produced in sufficientquantities to meet a patient's needs and must be supplied via externalsources. Handbook of Nonprescription Drugs, 11th edition, 1996, AmericanPharmaceutical Association. 2215 Constitution Avenue, NW, Washington,D.C. 20037. Chapter 19, Nutritional Products, page 361. In one aspect,many diets are insufficient in one or more key vitamins and supplementsare often indicated, especially in the cases of chronically illindividuals such as patients undergoing kidney dialysis. In one aspect,a vitamin can act as a cofactor to assist an enzyme in carrying out anessential biochemical reaction.

In one aspect, the formulations disclosed herein include one or morewater soluble vitamins. In one aspect, water-soluble vitamins aredepleted during kidney dialysis and should be replenished to maintainoverall health and well-being. In a further aspect, the supplementdisclosed herein provides water-soluble vitamins including the B complexvitamins and vitamin C.

B Complex Vitamins

In one aspect, the formulations disclosed herein include one or more Bvitamins. In this aspect, B vitamins generally act as cofactors orcoenzymes or precursors needed to make cofactors or coenzymes. In afurther aspect, B vitamins are not stored in the body and must beregularly supplied by dietary or other means to avoid deficiency. In oneaspect, co-supplementation of vitamins B₆, B₉, and B₁₂ along with ironis especially effective against osteoporosis and anemia while alsoimproving immune function. In a further aspect, all B complex vitaminscan be used instead of just one or two.

In another aspect, low levels of B vitamins can affect the manufactureof neurotransmitters and contribute to stress and anxiety. In thisaspect, supplementation of B vitamins can reduce stress related to theirdeficiency. In one aspect, low levels of B vitamins are caused bychronic kidney dialysis, the use of diuretics, and overconsumption ofrefined carbohydrates, since digestion of many carbohydrates requiresthe use of B vitamins. In one aspect, inadequate B vitamin intake islinked to blood sugar surges in patients who consume too many refinedcarbohydrates.

In one aspect, thiamin, or vitamin B₁, is included in the formulationsdisclosed herein. In this aspect, thiamin may be important to nerve andmuscle health, production of hydrochloric acid in the stomach, andtreatment of constipation and fatigue, as well as assisting digestion ofsome carbohydrates and proteins. In one aspect, the thiamine source isthiamine mononitrate. In one aspect, the amount of vitamin B₁ presentper unit dose is from 0.1 mg to 50 mg, 0.1 mg to 25 mg, 0.1 mg to 10 mg,0.1 mg to 5 mg, 0.1 mg to 2 mg, or 0.1 mg to 1 mg. In another aspect,0.5 mg to 2 mg of thiamine is present per unit dose of the supplement.

In another aspect, riboflavin, or vitamin B₂, is included in theformulations disclosed herein. In this aspect, riboflavin may beimportant for growth, red blood cell production, and eye health, as wellas assisting in the digestion of some carbohydrates, fats, ketonebodies, and proteins. In one aspect, the riboflavin source is molecularriboflavin. In one aspect, the amount of vitamin B₂ present per unitdose is from 0.1 mg to 2 mg, 0.5 mg to 2 mg, or 0.5 mg to 1 mg. Inanother aspect, 0.5 to 2 mg of riboflavin is present per unit dose ofthe supplement.

In still another aspect, nicotinic acid or nicotinamide, also known asniacinamide or vitamin B₃, is included in the formulations disclosedherein. Further in this aspect, vitamin B₃ is important to digestivesystem health and may assist in the digestion of some carbohydrates, aswell as in the production of various sex and stress-related hormones.Still further in this aspect, niacin may be useful in reducingcholesterol levels in the blood. In one aspect, the niacinamide sourceis molecular niacinamide. In one aspect, the amount of vitamin B₃present per unit dose is from 1 mg to 40 mg, 5 mg to 30 mg, or 5 mg to25 mg. In another aspect, 5 to 25 mg of niacinamide is present per unitdose of the supplement.

In one aspect, the formulations disclosed herein include pantothenicacid, or vitamin B₅. In this aspect, pantothenic acid may be importantfor red blood cells production, digestive system health, adrenal glandhealth, and the digestion of some carbohydrates. In one aspect, thepantothenate source is D-calcium pantothenate. In one aspect, the amountof vitamin B₅ present per unit dose is from 1 mg to 20 mg, 1 mg to 15mg, or 5 mg to 10 mg. In another aspect, 5 to 10 mg of L- or D-calciumpantothenate is present per unit dose of the supplement.

In another aspect, the formulations disclosed herein include pyridoxalphosphate (also occurring as pyridoxine), or vitamin B₆. Further in thisaspect, pyridoxal phosphate may be important for brain health and theproduction of red blood cells and immune system cells. In a furtheraspect, deficiencies in vitamin B₆ have been linked to diabetes, nervoussystem disorders, and heart disease. In one aspect, the pyridoxinesource is pyridoxine hydrochloride. In one aspect, the amount of vitaminB₆ present per unit dose is from 1 mg to 100 mg, 1 mg to 50 mg, or 1 mgto 10 mg. In another aspect, 1 to 10 mg of pyridoxine hydrochloride ispresent per unit dose of the supplement.

In still another aspect, the formulations disclosed herein includebiotin, or vitamin B₇. In a further aspect, biotin is important tovarious aspects of metabolism and may be important in strengthening thehair and nails as well as in the metabolism of fats and amino acids. Inone aspect, the biotin source is molecular biotin. In one aspect, theamount of vitamin B₇ present per unit dose is from 10 μg to 500 μg, 10μg to 300 μg, or 10 μg to 100 μg. In another aspect, 10 to 100 μg ofbiotin is present per unit dose of the supplement.

In one aspect, the formulations disclosed herein include folate, alsoknown as folic acid or vitamin B₉. Further in this aspect, folic acidmay be important for brain function, mental health, red blood cellsproduction, and production of nucleic acids. In one aspect, the folatesource is folic acid. In one aspect, the amount of vitamin B₉ presentper unit dose is from 0.05 mg to 1 mg, 0.1 mg to 1 mg, or 0.1 mg to 0.5mg. In another aspect, 0.2 to 0.4 mg of folic acid is present per unitdose of the supplement.

In another aspect, cobalamin, or vitamin B₁₂, is included in theformulations disclosed herein. Further in this aspect, the cobalamin maybe present as the cyanocobalamin, hydroxycobalamin, adenosylcobalamin,or methylcobalamin form. In another aspect, cobalamin is important tonervous system health, the production of red blood cells, and synthesisof nucleic acids. In a further aspect, cobalamin works synergisticallywith folate with respect to red blood cell production. In one aspect,the cobalamin source is cyanocobalamin. In one aspect, the amount ofvitamin B₁₂ present per unit dose is from 1 μg to 150 μg, 1 μg to 100μg, 1 μg to 50 μg, 1 μg to 25 μg, or 1 μg to 10 μg. In another aspect, 3to 6 μg of cyanocobalamin is present per unit dose of the supplement.

Vitamin C

In one aspect, the formulations disclosed herein include ascorbic acidor vitamin C. In a further aspect, vitamin C is important to the immunesystem, collagen production, and wound healing. Further in this aspect,vitamin C is needed for the biosynthesis of hydroxyproline, which isimportant in the synthesis of collagen, osteoid, and dentin.

In a further aspect, vitamin C is a potent antioxidant that can fightfree radical damage. In a still further aspect, vitamin C may assistwith the uptake of non-heme iron. In yet another aspect, vitamin C helpsto protect folate from oxidative damage.

In one aspect, the amount of vitamin C present per unit dose is from 10mg to 2,000 mg, 10 mg to 1,500 mg, 10 mg to 1,000 mg, 100 mg to 500 mg,or 100 mg to 300 mg. In another aspect, 100 to 300 mg of vitamin C (asascorbic acid) is provided per unit dose of the supplement.

Fat-soluble vitamins are absorbed in the small intestine and are storedin and can accumulate in body tissues. In some aspects, when excessivequantities of fat-soluble items are ingested, this can be toxic to thebody.

Vitamins A, E, and K

In one aspect, vitamins A, E, and K can accumulate to toxic levels inbody tissue of patients undergoing dialysis. Handbook of NonprescriptionDrugs, 11th edition, 1996, American Pharmaceutical Association. 2215Constitution Avenue, NW, Washington, D.C. 20037. Chapter 19, NutritionalProducts, page 366. Further in this aspect, supplementation of thesevitamins for kidney dialysis patients is contraindicated. In anotheraspect, the supplements disclosed herein do not include vitamins A, E,and K.

Vitamin D

In another aspect, vitamin D is a fat-soluble vitamin that is usuallyactivated by healthy or well-functioning kidneys. In one aspect, in thecase of kidney failure, the body cannot produce enough vitamin D and itshould be supplemented in patients with kidney failure. However, inanother aspect, a patient's medical providers may decide vitamin Dsupplementation is not required and/or would cause further harm. In anyof the above aspects, the supplement may or may not include a source ofvitamin D, to be given at the discretion of healthcare providers on acase-by-case basis.

In one aspect, when vitamin D is included in the formulations disclosedherein, it may improve bone health and immune system function and mayprotect against certain cancers. In a further aspect, vitamin D canincrease calcium and phosphate absorption from the small intestine, isimportant in bone mineralization, and maintains proper calcium andphosphorus levels in the serum. Handbook of Nonprescription Drugs, 11thedition, 1996, American Pharmaceutical Association. 2215 ConstitutionAvenue, NW, Washington, D.C. 20037. Chapter 19, Nutritional Products,page 368.

In one aspect, the amount of vitamin D present per unit dose is from 1μg to 100 μg, 1 μg to 50 μg, or 1 μg to 20 μg. In another aspect, 5 to10 μg of vitamin D (as cholecalciferol) are provided per unit dose ofthe supplements disclosed herein.

As used herein, a mineral is an inorganic element that is obtained fromfood or supplementation and is required for the functioning of the humanbody. Minerals include, but are not limited to, calcium, chromium,copper, iron, magnesium, manganese, molybdenum, nickel, potassium,selenium, sodium, vanadium, cobalt, and zinc. In one aspect, a mineralcan act as a cofactor. In other aspects, minerals can be used for cellsignaling, or can be an essential structural component of the body(e.g., calcium in bone), or can associate with proteins, nucleic acids,lipids, and carbohydrates to maintain particular secondary, tertiary,and quaternary structures.

In another aspect, the mineral can be part of a chelate complex.Chelates have a cyclic structure in which a central metallic ion is heldtight via covalent-coordinate bonds to form a coordinate compound, or, achelate complex. Furthermore, chelates occur abundantly in nature; forexample, chlorophyll complexed with magnesium, hemoglobin with iron,Vitamin B12 with cobalt hemocyanin with copper as well as enzymes thatcontain vanadium or molybdenum.

Chronic kidney dialysis can deplete the body of essential minerals. Inthis aspect, the supplements disclosed herein include a number ofimportant minerals.

Calcium

In one aspect, the formulations disclosed herein include apharmaceutically-acceptable compound of calcium. In a further aspect,calcium supplementation can be useful in preventing osteoporosis sincecalcium is a major component of bones and teeth. In a still furtheraspect, calcium's absorption and effects are enhanced or aided byvitamin D and parathyroid hormone. In still another aspect, calcium maybe important to B complex vitamin absorption and is important to thefunctional integrity of many cells. In yet another aspect, calciumrequirements may increase with increased protein consumption.

In one aspect, the calcium is provided as an ionic compound of calcium.Examples of such compounds include, but are not limited to, calciumcitrate, calcium citrate tetrahydrate, calcium lactate pentahydrate, andcalcium ascorbate. In one aspect, the formulations described hereininclude an ionic compound of calcium in an amount such that there is 100mg to 2,500 mg, 100 mg to 2,000 mg, 100 mg to 1,500 mg, 100 mg to 1,000mg, or 100 mg to 750 mg of calcium per unit dose. For example, calciumcitrate tetrahydrate has a molecular weight of 570.49, of which calciumis 21.08%. Thus, in order for the formulation to have 500 mg of calciumper unit dose, there will be approximately 2,372.3 mg of calcium citratetetrahydrate per unit dose. In another aspect, 250 to 500 mg of calciumis provided per unit dose of the supplements disclosed herein.

Magnesium

In one aspect, the formulations disclosed herein include apharmaceutically-acceptable compound of magnesium. In a further aspect,magnesium is necessary for the proper functioning of calcium in the bodysuch as, for example, assisting in entry of calcium ions into cells,thus preventing calcification of tissues. In some aspects, magnesiumsupplementation may support healthy heart function.

In one aspect, magnesium is required for normal bone structure formationand the functioning of several hundred enzymes, especially those withATP-dependent phosphorylation, protein synthesis, and carbohydratemetabolism. In a further aspect, magnesium in the extracellular matrixis important to electrical potentials in nerve and muscle cells and thetransmission of impulses across neuromuscular junctions.

In one aspect, the magnesium is provided as an ionic compound ofmagnesium. Examples of such compounds include, but are not limited to,magnesium citrate, magnesium sulfate monohydrate or heptahydrate,magnesium acetate tetrahydrate, magnesium D-gluconate hydrate, ormagnesium nitrate hexahydrate. In one aspect, the formulations describedherein include an ionic compound of magnesium in an amount such thatthere is 100 mg to 500 mg, 150 mg to 500 mg, 200 mg to 500 mg, 250 mg to500 mg, or 300 mg to 500 mg of magnesium per unit dose.

Zinc

In one aspect, the formulations disclosed herein include apharmaceutically-acceptable compound of zinc. In a further aspect, zincis especially depleted (from 40% to 78%) during dialysis. In someaspects, zinc is anti-inflammatory, anti-depressant, and functions tosupport the immune system. Handbook of Nonprescription Drugs, 11thedition, 1996, American Pharmaceutical Association. 2215 ConstitutionAvenue, NW, Washington, D.C. 20037. Chapter 19, Nutritional Products,page 388.

In another aspect, zinc is integral to the function of manymetalloenzymes and is a cofactor in the synthesis of nucleic acids. In afurther aspect, zinc is important in the mobilization of vitamin A fromthe liver and in several reproductive system hormones and functions inboth men and women.

In one aspect, the zinc is provided as an ionic compound of zinc.Examples of such compounds include, but are not limited to, zinccitrate, zinc citrate dihydrate, zinc acetate dihydrate, or zinc nitratehexahydrate. In one aspect, the formulations described herein include anionic compound of zinc in an amount such that there is 1 mg to 40 mg, 1mg to 30 mg, 1 mg to 20 mg, or 5 mg to 20 mg of zinc per unit dose.

Selenium

In one aspect, the formulations disclosed herein include apharmaceutically-acceptable compound of selenium. In a further aspect,selenium is highly concentrated in the liver and kidneys and is thusespecially depleted during dialysis. In a still further aspect, seleniumis a powerful antioxidant and is especially useful when employed againstthe damaging effects of free radicals. In another aspect, seleniumsupplementation may protect against hardening of the arteries andharmful molecules. Handbook of Nonprescription Drugs, 11th edition,1996, American Pharmaceutical Association. 2215 Constitution Avenue, NW,Washington, D.C. 20037. Chapter 19, Nutritional Products, page 387.

In one aspect, the selenium is provided as an ionic compound of seleniumsuch as, for example, sodium selenate. In one aspect, the formulationsdescribed herein include an ionic compound of selenium in an amount suchthat there is 10 μg to 400 μg, 10 μg to 300 μg, 10 μg to 200 μg, 10 μgto 100 μg, or 25 μg to 80 μg of selenium per unit dose.

Iron

In one aspect, the formulations disclosed herein include apharmaceutically-acceptable compound of iron. In a further aspect, ironis vital in preventing anemia. Handbook of Nonprescription Drugs, 11thedition, 1996, American Pharmaceutical Association. 2215 ConstitutionAvenue, NW, Washington, D.C. 20037. Chapter 19, Nutritional Products,page 380. In still another aspect, biochemically, iron is important tooxygen and electron transport as well as prevent anemia and improve thequality and quantity of red blood cells. In a further aspect, heme ironis found in meats and is well-absorbed, while non-heme iron is poorlyabsorbed. In a still further aspect, supplementation of iron may beparticularly important for patients consuming diets that include littleor no meat.

In one aspect, the iron is provided as an ionic compound of iron suchas, for example, iron gluconate, iron gluconate dihydrate, or ironsulfate heptahydrate. In one aspect, the formulations described hereininclude an ionic compound of iron in an amount such that there is 1 mgto 45 mg, 1 mg to 30 mg, 1 mg to 20 mg, or 5 mg to 20 mg of iron perunit dose.

In one aspect, the formulations disclosed herein incorporate one or moreamino acids. In a further aspect, these amino acids can be proteinogenicor non-proteinogenic.

L-Carnitine

L-carnitine is a vitamin-like molecule that is used by the body totransport fatty acids into the mitochondria for breakdown. It is anon-proteinogenic amino acid that is synthesized in the liver andkidneys from lysine and methionine. This essential amino acid iscompletely or almost completely depleted from the blood with chronickidney dialysis. L-carnitine deficiency has been linked to adversecardiac conditions including, but not limited to, arrhythmias andangina; thus, in one aspect, supplementing with L-carnitine can reducethe incidence of cardiac damage and cardiac events associated withkidney dialysis. In a further aspect, L-carnitine deficiency has beenshown to limit mitochondrial fat metabolism in the heart and otherorgans; in this aspect, supplementation with L-carnitine may helprestore normal mitochondrial fat metabolism. In still another aspect,L-carnitine supplementation can provide support in cases of muscleweakness and may protect against circulatory disorders. In a stillfurther aspect, L-carnitine has been shown to be important in oxidationof fatty acids and cellular energy management.

In one aspect, the formulations disclosed herein includepharmaceutically-acceptable compound of L-carnitine. Examples ofpharmaceutically-acceptable compounds of L-carnitine include, but arenot limited to, acetyl-L-carnitine or L-carnitine-L-tartrate, which canbe metabolized in the blood by plasma esterases to produce L-carnitine.In other aspects, L-carnitine can be used directly. In one aspect, theamount of the pharmaceutically-acceptable compound of L-carnitinepresent per unit dose is from 100 mg to 3,500 mg, 500 mg to 2,500 mg,500 mg to 1,000 mg, 1,000 mg to 2,000 mg of L-carnitine per unit dose.For example, 2,239 mg of L-carnitine-L-tartrate will provide 1,500 mg ofL-carnitine per unit dose. In a further aspect, 500 mg to 2,500 mg ofacetyl-L-carnitine or L-carnitine-L-tartrate is included in thesupplements disclosed herein.

In one aspect, depending on the patient needs as assessed by thehealthcare provider, additional ingredients can be included in thesupplements disclosed herein.

Citrus Bioflavonoids

In one aspect, the formulations disclosed herein include citrusbioflavonoids. In a further aspect, citrus fruits are excellent sourcesof vitamin C and citrus bioflavonoid preparations sourced from wholecitrus fruits or citrus rinds/peels or pith may be rich in vitamin C. Ina further aspect, the citrus bioflavonoids can be from lemons, limes,grapefruits, oranges, tangerines, or a combination thereof. In a furtheraspect, the citrus bioflavonoids can include rutin, quercetin,tangeritin, diosmetin, diosmin, naringin, nairrutin, neohesperidin,nobiletin, hesperidin, and combinations thereof.

In a still further aspect, citrus bioflavonoids may beanti-inflammatory, antioxidant, or anti-microbial. In still anotheraspect, citrus bioflavonoids may improve capillary permeability andcirculation, hypertension, swelling or edema, and insulin response, or acombination thereof. In still another aspect, sources of citrusbioflavonoids may contain flavor compounds that render the compositionsdisclosed herein more palatable.

Powdered Extract of Cranberry and Cherry

In one aspect, the formulations disclosed herein include powderedextracts of cranberry and cherry. In another aspect, cranberry andcherry extracts may contain flavor compounds that render thecompositions disclosed herein more palatable. In a further aspect,cranberry and cherry extracts are high in antioxidants, vitamins, andminerals.

In a still further aspect, cranberry extract contains D-mannose, a sugarthat has anti-biofilm (bacterial biofilm that is) properties, binds toand agglomerates bacteria in the urinary tract, thus helping to preventurinary tract infections, which can be especially important for dialysispatients.

In one aspect, the cherry extract is from tart cherry. Further in thisaspect, consumption of tart cherry extract may reduce side effects ofstatins, may improve blood cholesterol levels, may reduce inflammationrelated to arthritis and/or obesity, and may support a healthymetabolism.

In one aspect, some minerals are not to be included in the supplementsdisclosed herein.

Potassium

In one aspect, potassium is excluded from the formulations describedherein. In some aspects, high potassium levels can cause muscle andheart problems. In a further aspect, potassium levels can rise betweendialysis sessions and may affect the heartbeat.

Sodium

In another aspect, the formulations disclosed herein exclude sodium. Inone aspect, increased sodium consumption causes thirst and may lead towater retention. In a further aspect, excess sodium consumption and/orhigh sodium levels can raise the blood pressure.

Phosphorus

In one aspect, the formulations disclosed herein exclude phosphorus. Ina further aspect, too much phosphorus in the blood can cause calciumresorption from the bones. In still another aspect, too much phosphoruscan cause the skin to itch. Handbook of Nonprescription Drugs, 11thedition, 1996, American Pharmaceutical Association. 2215 ConstitutionAvenue, NW, Washington, D.C. 20037. Chapter 19, Nutritional Products,page 383-384. In one aspect, a phosphate binder is provided to thepatient alongside the formulations disclosed herein.

The supplements described herein can be formulated using techniquesknown in the art. In one aspect, the minerals, vitamins, and amino acidssupplied in dry form are admixed with one another to produce a drypowder. In addition to the minerals, vitamins, and amino acids, otherpharmaceutically-acceptable fillers can be added to formulate thesupplement in powder form. For example, polysaccharides such as, forexample, maltodextrin, can be used to formulate the supplement.

In one aspect, the supplement is a unit dose composition composed of

-   -   (a) vitamin B1    -   (b) vitamin B2    -   (c) vitamin B3    -   (d) vitamin B5    -   (e) vitamin B6    -   (f) vitamin B7    -   (g) vitamin B9    -   (h) vitamin B12    -   (i) vitamin C    -   (j) vitamin D₃    -   (k) a pharmaceutically-acceptable compound of calcium    -   (l) a pharmaceutically-acceptable compound of magnesium    -   (m) a pharmaceutically-acceptable compound of zinc    -   (n) a pharmaceutically-acceptable compound of selenium    -   (o) a pharmaceutically-acceptable compound of iron    -   (p) a pharmaceutically-acceptable compound of L-carnitine.

In another aspect, the supplement includes the following components in adry powder:

-   -   (a) vitamin B1 in the amount of 0.1 mg to 50 mg per unit dose;    -   (b) vitamin B2 in the amount of 0.1 mg to 2 mg per unit dose;    -   (c) vitamin B3 in the amount of 1 mg to 40 mg per unit dose;    -   (d) vitamin B5 in the amount of 1 mg to 20 mg per unit dose;    -   (e) vitamin B6 in the amount of 1 mg to 100 mg per unit dose;    -   (f) vitamin B7 in the amount of 10 μg to 500 μg per unit dose;    -   (g) vitamin B9 in the amount of 0.05 mg to 1.0 mg per unit dose;    -   (h) vitamin B12 in the amount of 1 μg to 150 μg per unit dose;    -   (i) vitamin C in the amount of 10 mg to 2,000 mg per unit dose;    -   (j) vitamin D₃ in the amount of 1 μg to 100 μg per unit dose;    -   (k) a pharmaceutically-acceptable compound of calcium in the        amount of 100 mg to 2,500 mg per unit dose;    -   (l) a pharmaceutically-acceptable compound of magnesium in the        amount of 100 mg to 500 mg per unit dose;    -   (m) a pharmaceutically-acceptable compound of zinc in the amount        of 1 mg to 40 mg per unit dose;    -   (n) a pharmaceutically-acceptable compound of selenium in the        amount of 10 μg to 400 μg per unit dose;    -   (o) a pharmaceutically-acceptable compound of iron in the amount        of 1 mg to 45 mg per unit dose; and    -   (p) a pharmaceutically-acceptable compound of L-carnitine in the        amount of 100 mg to 3,500 mg per unit dose.

In another aspect, the supplement includes the following components in adry powder:

-   -   (a) vitamin B1 in the amount of 0.5 mg to 2 mg per unit dose;    -   (b) vitamin B2 in the amount of 0.5 mg to 2 mg per unit dose;    -   (c) vitamin B3 in the amount of 1 mg to 20 mg per unit dose;    -   (d) vitamin B5 in the amount of 1 mg to 15 mg per unit dose;    -   (e) vitamin B6 in the amount of 1 mg to 10 mg per unit dose;    -   (f) vitamin B7 in the amount of 10 g to 100 μg per unit dose;    -   (g) vitamin B9 in the amount of 0.1 mg to 1.0 mg per unit dose;    -   (h) vitamin B12 in the amount of 1 μg to 10 μg per unit dose;    -   (i) vitamin C in the amount of 100 mg to 300 mg per unit dose;    -   (j) vitamin D₃ in the amount of 1 μg to 20 μg per unit dose;    -   (k) a pharmaceutically-acceptable compound of calcium in the        amount of 100 mg to 1,000 mg per unit dose;    -   (l) a pharmaceutically-acceptable compound of magnesium in the        amount of 100 mg to 500 mg per unit dose;    -   (m) a pharmaceutically-acceptable compound of zinc in the amount        of 5 mg to 20 mg per unit dose;    -   (n) a pharmaceutically-acceptable compound of selenium in the        amount of 10 μg to 100 μg per unit dose;    -   (o) a pharmaceutically-acceptable compound of iron in the amount        of 5 mg to 30 mg per unit dose; and    -   (p) L-carnitine-L-tartrate in the amount of 1,000 mg to 3,000 mg        per unit dose.

In another aspect, the supplement has the following components asprovided in Table 1.

TABLE 1 Formulation of a Representative Nutritional Supplement AmountPer Component Unit Dose Source Vitamin B₁ 1.5 mg Thiamine MononitrateVitamin B₂ 1.7 mg Riboflavin Vitamin B₃ 20 mg Niacinamide Vitamin B₅ 10mg D-Calcium Pantothenate Vitamin B₆ 15 mg Pyridoxine HydrochlorideVitamin B₇ 100 μg Biotin Vitamin B₉ 1 mg Folic Acid Vitamin B₁₂ 6 μgCyanocobalamin Vitamin C 250 mg Ascorbic Acid Vitamin D₃ 10 μgCholecalciferol Calcium 500 mg Calcium Citrate Magnesium 400 mgMagnesium Citrate Zinc 15 mg Zinc Citrate Selenium 70 μg Sodium SelenateIron 18 mg Iron Gluconate Marine Omega 3 1000 mg Wild Alaskan Salmon Oilor Fatty Acids Marine Algal Oil, EPA:DHA ratio is from 1:1 to 4:1.L-Carnitine 1500 mg Acetyl-L-Carnitine or L-Carnitine-L-TartrateCoenzyme Q10H2 200 mg Ubiquinol Turmeric 2 g (optional) Ground Spice orExtract Citrus Bioflavonoids (optional) Ground Rind or Extract Extractof Cranberry (optional) Extract of Dried, Powdered and Cherry PowdersFruits

The supplements described herein are intended to be taken orally. In oneaspect, the supplements can be formulated as tablets or capsules. Inother aspects, the supplements can be formulated as a powder that can bemixed with water or another beverage. Alternatively, the powder form ofthe supplement can be admixed with food such as yogurt, peanut butter,or other foods that readily mix with the supplement.

The formulations described herein are to be administered to patientswith kidney disease and/or undergoing kidney dialysis, or individuals atrisk of kidney diseases (lifestyle, family history, etc.). The amount offormulation administered to the patient should not exceed therecommended daily dose for each component. The formulations can beadministered to the patient prior to dialysis, during dialysis, afterdialysis, and any combination thereof. The nutritional supplementdescribed herein is designed to support kidney and cardiac function aswell as mitochondrial energy function needs in patients undergoinghemodialysis. This supplement replenishes essential vitamins andminerals that are lost during dialysis, does not contain compounds thatmay specifically cause harm to dialysis patients, and provides supportfor tissues undergoing oxidative stress. By replenishing the mineralsand vitamins lost during dialysis, the subject will have increasedenergy levels that will permit the subject to lead a more productivelife.

One or more additional supplements can be taken with the supplementsdescribed herein. In one aspect, an omega 3 fatty acid can be taken withthe supplements described herein. Omega 3 fatty acids are lipid solublemacronutrients that are important to metabolism (i.e., energy productioncaptured in the form of ATP). Omega 3 fatty acids are partially removedfrom the body with chronic kidney dialysis. Omega 3 fatty acids havebeen shown to reduce inflammation and thus to lower the risk of chronicdiseases (including heart disease). They are believed to be importantfor cognitive function and also have been shown to reduce triglycerideswhile increasing high-density lipoproteins (HDL) cholesterol. Omega 3fatty acids have been linked to improvement in a number of otherconditions including from skin, joint, eye, and gastrointestinalconditions. In one aspect, supplementation with omega 3 fatty acids canbe especially important for improving blood pressure, blood circulation,and blood vessel elasticity while preventing cardiovascular and coronaryevents in persons with high cardiovascular risk. Marine Omega 3 FattyAcids: https://en.wikipedia.orq/wiki/Fatty acid metabolism

Omega 3 fatty acids are found in fish, some plants, nut oils, and algae,and are not always consumed in high enough amounts through the standarddiet. In one aspect, it is important to replenish the body's supply ofomega 3 fatty acids, since these important macronutrients cannot besynthesized by the body. In another aspect, marine omega 3 fatty acids(i.e., from fish or algae) have preferable amounts of DHA(docosahexaenoic acid) and EPA (eicosapentaenoic acid) as compared toomega 3 fatty acids from plant sources, which primarily contain ALA(alpha linolenic acid), a compound that is not efficiently utilized bythe body.

In still another aspect, the formulations disclosed herein includemarine omega 3 fatty acids. In a further aspect, the marine omega 3fatty acids can be sourced from salmon, mackerel, sardines, tuna, orherring. Many Western diets incorporate higher dietary omega 6 fattyacids, which can promote inflammation. In another aspect, it isimportant to supplement omega 3 fatty acids, especially in hemodialysispatients, to reduce inflammation and the risk of death. In anotheraspect, the amount of Omega 3 is significantly higher than the amountOmega 6.

In yet another aspect, hemodialysis is believed to upregulate oxidativemechanisms, which could lead to peroxidation of omega 3 fatty acids;this, in turn, can lead to breakdown of the fatty acid structure andloss of function. In this aspect, supplementation with omega 3 fattyacids can be used to replenish the supply of nutrients destroyed byperoxidation.

In one aspect, the marine omega 3 fatty acids are provided as wildAlaskan salmon oil or marine algal oil. In a further aspect, the EPA:DHAratio of the marine omega 3 fatty acids is from 1:1 to 4:1. In oneaspect, the amount of marine omega 3 fatty acids present per unit doseis from 500 mg to 4,000 mg, 500 mg to 3,000 mg, 500 mg to 2,000 mg, or500 mg to 1,500 mg. In another aspect, 1000 mg of marine omega 3 fattyacids are provided per unit dose of the supplements disclosed herein.

In another aspect, coenzyme Q10 (CoQ10) can be taken with thesupplements described herein. CoQ10 acts as an antioxidant and protectsthe cell membrane against oxidative stress. In another aspect, CoQ10 isan important coenzyme in the mitochondria (and other parts of the cell)and participates in cellular respiration, which ultimately generatesenergy in the form of adenosine triphosphate. In still another aspect,CoQ10 protects against low-density lipoproteins (LDL) oxidation, whichis vital for heart health. In a further aspect, reduced form of CoQ10(CoQ10H₂) can regenerate vitamin E from the alpha-tocopheroxyl radical,thus leading to a reduction of oxidative stress.

In one aspect, certain patients require intake of CoQ10 that is higherthan provided by the average diet. These include, but are not limitedto, athletes, patients with hyperthyroidism, patients who are takingstatins, and the elderly. Thus, in one aspect, elderly dialysis patientsmay especially benefit from CoQ10 supplementation. In a related aspect,CoQ10 can decrease insulin requirements in patients with diabetes; thus,diabetic dialysis patients may also benefit from CoQ10 supplementation.

In another aspect, however, CoQ10 supplementation should be avoided inpatients taking warfarin or other blood thinners, as it can reduce theactivity of these medications. In this aspect, the supplements disclosedherein do not include CoQ10.

In one aspect, CoQ10 in the supplements disclosed herein is provided asubiquinol, a reduced form of CoQ10 that has a particularly high uptakepercentage and subsequently leads to an increase of CoQ10 levels in theblood. Ubiquinol effectively regenerates vitamin E from alpha-tocopherolradical. In one aspect, the amount of CoQ10H₂ (e.g., ubiquinol) presentper unit dose is from 70 mg to 400 mg, 70 mg to 300 mg, or 150 mg to 250mg. In another aspect, 200 mg of ubiquinol are included in thesupplements disclosed herein.

In one aspect, turmeric can be taken with the supplements describedherein. Turmeric has anti-inflammatory and antioxidant properties thatare in some aspects useful to the kidneys. In another aspect, theformulations disclosed herein do not include turmeric. In some aspects,turmeric should not be given to patients who are sensitive or allergic,pregnant or nursing, diabetic and taking blood thinners, patients withgall bladder conditions, and/or patients with digestive system disorderssuch as GERD (gastroesophageal reflux disease). In one aspect, turmericis prepared in a separate distribution form (e.g., a separate capsule)and given to patients at their healthcare providers' discretion. Instill another aspect, turmeric is provided with the supplement unlessthe patient is going to undergo surgery and/or has a bleeding disorder,since turmeric is known to be a powerful blood thinner.

In one aspect, pepperine can be taken with the supplements describedherein. In some aspects, turmeric is not easily absorbed by the body andpepperine enhances absorption by 10 to 20 fold. In one aspect, theformulations disclosed herein include 100 mg of pepperine for every 500mg of turmeric. In one aspect, the amount of turmeric present per unitdose is from 1 g to 3 g, 1.5 g to 2.5 g, or 2 g.

In one aspect, the supplements is formulated as a kit, where onecompartment or vial has a mixture of the supplement described hereincomposed of the minerals, vitamins, and amino acids supplied in dry form(e.g., tablet, powder), and a second compartment of containing othersupplements (e.g., marine omega 3 fatty acids in capsule form, ubiquinolin gel form, turmeric is in a capsule, or any combination thereof).

EXAMPLES

The following examples are put forth so as to provide those of ordinaryskill in the art with a complete disclosure and description of how thematerials, articles, and methods described and claimed herein are madeand evaluated, and are intended to be purely exemplary and are notintended to limit the scope of what the inventors regard as theirinvention. Efforts have been made to ensure accuracy with respect tonumbers (e.g., amounts, temperature, etc.) but some errors anddeviations should be accounted for. Unless indicated otherwise, partsare parts by weight, temperature is in ° C. or is at ambienttemperature, and pressure is at or near atmospheric. There are numerousvariations and combinations of reaction conditions, e.g., componentconcentrations, desired solvents, solvent mixtures, temperatures,pressures and other reaction ranges and conditions that can be used tooptimize the product purity and yield obtained from the describedprocess. Only reasonable and routine experimentation will be required tooptimize such process conditions.

The components in Table 2 were admixed with one another in dry form toproduce a supplement. Maltodextrin was added in an amount so that 8.5 gof supplement was produced.

TABLE 2 Amount Per Component Unit Dose Source Vitamin B₁ 1.5 mg ThiamineMononitrate Vitamin B₂ 1.7 mg Riboflavin Vitamin B₃ 20 mg Niacin VitaminB₅ 10 mg D-Calcium Pantothenate Vitamin B₆ 5 mg Pyridoxine HydrochlorideVitamin B₇ 0.1 mg Biotin Vitamin B₉ 0.4 mg Folic Acid Vitamin B₁₂ 6 μgCyanocobalamin Vitamin C 250 mg Ascorbic Acid Vitamin D₃ 10 μgCholecalciferol Calcium 500 mg Calcium Citrate Magnesium 400 mgMagnesium Citrate Zinc 15 mg Zinc Citrate Selenium 70 μg Sodium SelenateIron 18 mg Iron Gluconate L-Carnitine 1500 mg L-Carnitine-L-Tartrate(2239 mg) Citrus Bioflavonoids 50 mg

A supplement described herein was evaluated with a subject undergoingdialysis. The subject has been treated for dialysis for the last 20years and for the last 13 years at his home. Dialysis is conducted athome every other night for 7 hours.

The subject initially started taking a full dose of the supplements (8.5g of the supplement provided in Table 2). However, the doze of thesupplement was adjusted to a half dose. The subject took a quarter ofthe supplement together with fast carbohydrates for breakfast and thesame dose for lunch with fast carbohydrates.

After three weeks, the subject's mental condition improved. The subjectdid not need to sleep so much as before. The subject has more energy andis able to do more activities such as play golf.

After taking the supplement for about six weeks, the subject has moreenergy and able to perform more outdoor activities (e.g., play 18 holesof golf).

The subject perspires much more compared to when he was not taking thesupplement, which is positive for dialysis patients that have problemsgetting rid of excess liquid in their body. The subject is also sleepingvery well and is more focused. The subject's blood pressure is good.Renal blood samples are also good except for the level of sodium, whichhas been adjusted due to dialysis treatment.

Throughout this publication, various publications are referenced. Thedisclosures of these publications in their entireties are herebyincorporated by reference into this application in order to more fullydescribe the methods, compositions, and compounds herein.

Various modifications and variations can be made to the materials,methods, and articles described herein. Other aspects of the materials,methods, and articles described herein will be apparent fromconsideration of the specification and practice of the materials,methods, and articles disclosed herein. It is intended that thespecification and examples be considered as exemplary.

What is claimed:
 1. A unit dose composition comprising (a) vitamin B1(b) vitamin B2 (c) vitamin B3 (d) vitamin B5 (e) vitamin B6 (f) vitaminB7 (g) vitamin B9 (h) vitamin B12 (i) vitamin C (j) vitamin D₃ (k) apharmaceutically-acceptable compound of calcium (l) apharmaceutically-acceptable compound of magnesium (m) apharmaceutically-acceptable compound of zinc (n) apharmaceutically-acceptable compound of selenium (o) apharmaceutically-acceptable compound of iron (p) apharmaceutically-acceptable compound of L-carnitine.
 2. The compositionof claim 1, wherein the composition comprises (a) vitamin B1 in theamount of 0.1 mg to 50 mg per unit dose; (b) vitamin B2 in the amount of0.1 mg to 2 mg per unit dose; (c) vitamin B3 in the amount of 1 mg to 40mg per unit dose; (d) vitamin B5 in the amount of 1 mg to 20 mg per unitdose; (e) vitamin B6 in the amount of 1 mg to 100 mg per unit dose; (f)vitamin B7 in the amount of 10 μg to 500 μg per unit dose; (g) vitaminB9 in the amount of 0.05 mg to 1.0 mg per unit dose; (h) vitamin B12 inthe amount of 1 μg to 150 μg per unit dose; (i) vitamin C in the amountof 10 mg to 2,000 mg per unit dose; (j) vitamin D₃ in the amount of 1 μgto 100 μg per unit dose; (k) a pharmaceutically-acceptable compound ofcalcium in the amount of 100 mg to 2,500 mg per unit dose; (l) apharmaceutically-acceptable compound of magnesium in the amount of 100mg to 500 mg per unit dose; (m) a pharmaceutically-acceptable compoundof zinc in the amount of 1 mg to 40 mg per unit dose; (n) apharmaceutically-acceptable compound of selenium in the amount of 10 μgto 400 μg per unit dose; (o) a pharmaceutically-acceptable compound ofiron in the amount of 1 mg to 45 mg per unit dose; (p) apharmaceutically-acceptable compound of L-carnitine in the amount of 100mg to 3,500 mg per unit dose.
 3. The composition of claim 1, wherein thepharmaceutically-acceptable compound of L-carnitine isL-carnitine-L-tartrate or acetyl-L-carnitine.
 4. The composition ofclaim 1, wherein the calcium is calcium citrate, the magnesium ismagnesium citrate, the zinc is zinc citrate; the sodium is sodiumselenate; and the iron is iron gluconate.
 5. The composition of claim 1,wherein the composition further comprises a citrus bioflavonoid, apowdered extract of cranberry and/or cherry, or a combination thereof.6. The composition of claim 1, wherein the composition comprises a drypowder.
 7. The composition of claim 1, wherein the composition comprises(a) vitamin B1 in the amount of 0.5 mg to 2 mg per unit dose; (b)vitamin B2 in the amount of 0.5 mg to 2 mg per unit dose; (c) vitamin B3in the amount of 1 mg to 20 mg per unit dose; (d) vitamin B5 in theamount of 1 mg to 15 mg per unit dose; (e) vitamin B6 in the amount of 1mg to 10 mg per unit dose; (f) vitamin B7 in the amount of 10 g to 100μg per unit dose; (g) vitamin B9 in the amount of 0.1 mg to 1.0 mg perunit dose; (h) vitamin B12 in the amount of 1 μg to 10 μg per unit dose;(i) vitamin C in the amount of 100 mg to 300 mg per unit dose; (j)vitamin D₃ in the amount of 1 μg to 20 μg per unit dose; (k) apharmaceutically-acceptable compound of calcium in the amount of 100 mgto 1,000 mg per unit dose; (l) a pharmaceutically-acceptable compound ofmagnesium in the amount of 100 mg to 500 mg per unit dose; (m) apharmaceutically-acceptable compound of zinc in the amount of 5 mg to 20mg per unit dose; (n) a pharmaceutically-acceptable compound of seleniumin the amount of 10 μg to 100 μg per unit dose; (o) apharmaceutically-acceptable compound of iron in the amount of 5 mg to 30mg per unit dose; and (p) L-carnitine-L-tartrate in the amount of 1,000mg to 3,000 mg per unit dose.
 8. The composition of claim 1, wherein thecomposition does not include a pharmaceutically-acceptable compound ofpotassium, sodium, or phosphorous.
 9. A kit comprising (a) thecomposition of claim 1; and (b) a capsule comprising marine omega 3fatty acids, a gel comprising coenzyme Q10, or a combination thereof.10. The kit of claim 9, wherein the marine omega 3 fatty acids compriseDHA and EPA in the weight ratio (EPA:DHA) of 1:1 to 4:1.
 11. The kit ofclaim 9, wherein the marine omega 3 fatty acids are in the amount of 500mg to 4,000 mg per unit dose.
 12. The kit of claim 9, wherein coenzymeQ10 is ubiquinol.
 13. The kit of claim 9, wherein the coenzyme Q10 is inthe amount of 70 mg to 400 mg per unit dose.
 14. The kit of claim 9,wherein the kit further comprises a capsule comprising turmeric, whereinthe turmeric is in the amount of 1 g to 3 g per unit dose.
 15. The kitof claim 9, wherein the dry component in component (a) comprises (a)vitamin B1 in the amount of 0.1 mg to 50 mg per unit dose; (b) vitaminB2 in the amount of 0.1 mg to 2 mg per unit dose; (c) vitamin B3 in theamount of 1 mg to 40 mg per unit dose; (d) vitamin B5 in the amount of 1mg to 20 mg per unit dose; (e) vitamin B6 in the amount of 1 mg to 100mg per unit dose; (f) vitamin B7 in the amount of 10 μg to 500 μg perunit dose; (g) vitamin B9 in the amount of 0.05 mg to 1.0 mg per unitdose; (h) vitamin B12 in the amount of 1 μg to 150 μg per unit dose; (i)vitamin C in the amount of 10 mg to 2,000 mg per unit dose; (j) vitaminD₃ in the amount of 1 μg to 100 μg per unit dose; (k) apharmaceutically-acceptable compound of calcium in the amount of 100 mgto 2,500 mg per unit dose; (l) a pharmaceutically-acceptable compound ofmagnesium in the amount of 100 mg to 500 mg per unit dose; (m) apharmaceutically-acceptable compound of zinc in the amount of 1 mg to 40mg per unit dose; (n) a pharmaceutically-acceptable compound of seleniumin the amount of 10 μg to 400 μg per unit dose; (o) apharmaceutically-acceptable compound of iron in the amount of 1 mg to 45mg per unit dose; (a) a pharmaceutically-acceptable compound ofL-carnitine in the amount of 100 mg to 3,500 mg per unit dose.
 16. Thekit of claim 15, wherein the pharmaceutically-acceptable compound ofL-carnitine is L-carnitine-L-tartrate or acetyl-L-carnitine.
 17. The kitof claim 15, wherein the calcium is calcium citrate, the magnesium ismagnesium citrate, the zinc is zinc citrate; the sodium is sodiumselenate; and the iron is iron gluconate.
 18. The kit of claim 15,wherein the composition further comprises a citrus bioflavonoid, apowdered extract of cranberry and/or cherry, or a combination thereof.19. The kit of claim 9, wherein the dry component in component (a)comprises (a) vitamin B1 in the amount of 0.5 mg to 2 mg per unit dose;(b) vitamin B2 in the amount of 0.5 mg to 2 mg per unit dose; (c)vitamin B3 in the amount of 1 mg to 20 mg per unit dose; (d) vitamin B5in the amount of 1 mg to 15 mg per unit dose; (e) vitamin B6 in theamount of 1 mg to 10 mg per unit dose; (f) vitamin B7 in the amount of10 g to 100 μg per unit dose; (g) vitamin B9 in the amount of 0.1 mg to1.0 mg per unit dose; (h) vitamin B12 in the amount of 1 μg to 10 μg perunit dose; (i) vitamin C in the amount of 100 mg to 300 mg per unitdose; (j) vitamin D₃ in the amount of 1 μg to 20 μg per unit dose; (k) apharmaceutically-acceptable compound of calcium in the amount of 100 mgto 1,000 mg per unit dose; (l) a pharmaceutically-acceptable compound ofmagnesium in the amount of 100 mg to 500 mg per unit dose; (m) apharmaceutically-acceptable compound of zinc in the amount of 5 mg to 20mg per unit dose; (n) a pharmaceutically-acceptable compound of seleniumin the amount of 10 μg to 100 μg per unit dose; (o) apharmaceutically-acceptable compound of iron in the amount of 5 mg to 30mg per unit dose; and (a) L-carnitine-L-tartrate in the amount of 1,000mg to 3,000 mg per unit dose.
 20. The kit of claim 9, wherein the drypowder in component (a) does not include a pharmaceutically-acceptablecompound of potassium, sodium, or phosphorous.